Organ preservation and/or perfusion solution

Abstract

Serum albumin is an important molecule in human and animal blood. It provides oncotic pressure and acts as a transportation agent, delivering nutrients from the blood to the tissue and removing waste products from the tissue to the blood. This invention describes an organ preservation and/or perfusion solution which comprises acetylated serum albumin, as well as method of making and using such a solution, and uses of acetylated serum albumin itself. The acetylated serum albumin utilised in the present invention can protect the vascular endothelium during perfusion of an isolated organ or tissue.

The invention claimed is: 
     
         1 . A method of use of an organ preservation and/or perfusion solution in isolated organ or tissue perfusion comprising a step of perfusing an isolated organ or tissue with the organ preservation and/or perfusion solution, wherein:
 the organ preservation and/or perfusion solution comprises acetylated serum albumin and glucose; and   the acetylated serum albumin has been formed by acetylation of serum albumin with acetylsalicylic acid with incubation in vitro for at least 12 hours.   
     
     
         2 . The method of use according to  claim 1 , wherein the isolated organ is circulatorily isolated in vivo or is circulatorily isolated ex vivo. 
     
     
         3 . The method of use according to  claim 1 , wherein the isolated organ is a lung or lungs, a heart, a kidney, a liver, a pancreas, intestines or a limb or limbs. 
     
     
         4 . The method of use according to  claim 1 , wherein if the organ is transplanted, it is not transplanted into the body from which it came. 
     
     
         5 . The method of use according to  claim 1 , wherein the step of perfusing the isolated organ or tissue with the organ preservation and/or perfusion solution protects the vascular endothelium and/or reduces vascular resistance. 
     
     
         6 . The method of use according to  claim 1 , wherein the organ preservation and/or perfusion solution is sterilized. 
     
     
         7 . The method of use according to  claim 1 , wherein the serum albumin has also been loaded with a compound that binds to or reacts with the serum albumin, wherein the compound is selected from: a fatty acid molecule; a fat soluble vitamin; an antioxidant; a hormone; a trace element; a pharmaceutical; an NO donor; or combinations thereof. 
     
     
         8 . The method of use according to  claim 7 , wherein the compound that binds to or reacts with the serum albumin is:
 a fatty acid which is a nitroalkene derivative of oleic acid, 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) or sphingosine-1-phosphate (S1P);   a fat soluble vitamin which is retinoic acid (vitamin A), cholecalciferol (vitamin D3), alpha-tocopherol (vitamin E) or vitamin K;   a hydrophobic pharmaceutical which is a thrombin inhibitor;   an antioxidant which is 2-mercaptopropionylglycine (MPG) or glutathione;   a hormone, which is cortisone, prednisolone, triiodothyronine, melatonin or somapacitan;   a trace element which is copper or nickel;   a pharmaceutical which is thrombin, argatroban, or clenbuterol;   an NO donor, which is a thionitrites, S-nitrosoglutathion (GSNO) or arginine; or   combinations thereof.   
     
     
         9 . The method of use according to  claim 1 , wherein the serum albumin is a mammalian serum albumin. 
     
     
         10 . The method of use according to  claim 1 , wherein the organ preservation and/or perfusion solution also comprises dextran, calcium ions, a buffer, and water. 
     
     
         11 . The method of use according to  claim 1 , wherein the organ preservation and/or perfusion solution has a pH of 6.6 to 7.8. 
     
     
         12 . The method of use according to  claim 1 , wherein the organ preservation solution has a glucose concentration of 5 to 8 nM. 
     
     
         13 . The method of use according to  claim 1 , wherein the serum albumin is purified recombinant serum albumin or is cleaned prior to being mixed with acetylsalicylic acid. 
     
     
         14 . The method of use according to  claim 1 , wherein the molar ratio of serum albumin to acetylsalicylic acid in the organ preservation and/or perfusion solution is between 1:2 and 2:1. 
     
     
         15 . The method of use according to  claim 1 , wherein the organ preservation and/or perfusion solution is ready to use. 
     
     
         16 . The method of use according to  claim 1 , wherein the acetylated serum albumin has been formed by acetylation of serum albumin with acetylsalicylic acid with incubation in vitro for at least 12 hours in the presence of glucose. 
     
     
         17 . The method of use according to  claim 1 , wherein the acetylated serum albumin has been formed by acetylation of serum albumin with acetylsalicylic acid with incubation in vitro for at least 12 hours in the absence of glucose. 
     
     
         18 . The method of use according to  claim 1 , wherein the acetylated serum albumin has been formed by acetylation of serum albumin with acetylsalicylic acid with incubation in vitro for at least 12 hours at 25° C. or at least 24 hours at 2 to 8° C.